Angiotensin-converting enzyme 2 is an essential regulator of heart function
| Autor: | Liyong Zhang, Joan da Costa, Ivona Kozieradzki, Michael A. Crackower, Gavin Y. Oudit, Armen S. Manoukian, Josef M. Penninger, James W. Scholey, York Pei, Sam E. Scanga, Yoram Yagil, Chana Yagil, Antonio J. Oliveira-dos-Santos, Renu Sarao, Mark C. Chappell, Carlos M. Ferrario, Peter H. Backx |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Heart morphogenesis Candidate gene X Chromosome Mutant Blood Pressure Peptidyl-Dipeptidase A Biology Quantitative trait locus Gene Expression Regulation Enzymologic Mice Quantitative Trait Heritable Gene expression Animals Drosophila Proteins Cloning Molecular Hypoxia Mice Knockout Regulation of gene expression Genetics Radiation Hybrid Mapping Multidisciplinary Angiotensin II Myocardium Metalloendopeptidases Heart Myocardial Contraction Rats Up-Regulation Cell biology Drosophila melanogaster Hypertension Angiotensin-converting enzyme 2 Female Gene Deletion hormones hormone substitutes and hormone antagonists |
| Zdroj: | Nature. 417:822-828 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature00786 |
| Popis: | Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo. |
| Databáze: | OpenAIRE |
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